In vivo imaging techniques are now essential in medical settings. An exemplary method involves administering 5-aminolevulinic acid (ALA) to a cancer patient and detecting the red emission of its metabolite protoporphyrin IX (PPIX) by blue light excitation to confirm the outline of ill-defined tumor. This method is used in order to assist surgical operation.
Such a method for locally diagnosing tumor by use of fluorescence generated by a light-sensitive substance accumulated in tumor is called photodynamic diagnosis (PDD). Upon excitation, PPIX further generates active oxygen called singlet oxygen, which can in turn destroy cancer tissues. The blue light excitation, however, merely causes the destruction of cancer tissues located in the surface due to its low tissue penetration. Accordingly, use of excitation light having higher tissue penetration can be expected to produce therapeutic effects. Use of near-infrared light (NIR) can overcome not only low tissue penetration but the problems of background fluorescence from excitation in ultraviolet to visible light regions and phototoxicity. Lanthanide nanoparticles (LNP) are known as a tool that achieves this NIR excitation having various advantages (see for example, patent document 1). Usual fluorescent groups emit light with lower energy than that of excitation light, whereas LNP emits, by NIR excitation, visible light with higher energy. This upconversion luminescence is receiving attention.
For example, an antibody-LNP complex having a cancer antigen-specific antibody bonded to the surface of a silica layer doped with the photosensitizing dye merocyanine 540 and coated on LNP (NaYF4; Yb3+,Er3+) (see for example, non-patent document 1) and a fine phosphor particle-organic dye complex in which a porphyrin dye having a terminal carboxyl group is bonded via an amide bond to the surface of a rare-earth element-containing fine phosphor particle that emits upconversion luminescence, wherein the complex attains a deep body penetration and is suitable for a photodynamic therapy method, etc. (see for example, patent document 2) have been proposed as photodynamic therapy (PDT) using such upconversion luminescence.